PO-02-240 IMPACTS OF DAPAGLIFLOZIN ON STRUCTURAL REMODELING AND ARRHYTHMOGENICITY IN CARDIORENAL SYNDROME

Abstract

Chronic kidney disease (CKD) patients revealed cardiac structural and electrical remodeling. The interaction between the heart and kidney leads to cardiorenal syndrome. Dapagliflozin (DAPA) reduces cardiovascular (CV) events in heart failure (HF). However, the efficacy of DAPA on cardiorenal syndrome is questionable. We aimed to investigate the electrophysiology (EP) properties and cardiac reverse remodeling of dapagliflozin in CKD rabbits with HF. Eighteen New Zealand white rabbits were randomized into the sham (n=6), CKD (n=6), CKD-DAPA (n=6) groups. The rabbits in the CKD and CKD-DAPA groups were created by 5/6 nephrectomy method with follow-up echocardiogram to confirm HF. The CKD-DAPA group received oral dapagliflozin 1 mg/kg/day for 4 weeks. All rabbits received an echocardiogram, blood samples, and EP study. Myocardium was harvested for Trichrome stain. The creatinine levels of the CKD and CKD-DAPA levels were significantly higher than those in the sham group (2.31±0.21 vs. 1.32±0.11 mg/dL; 2.29±0.13 vs. 1.32±0.11 mg/dL, both p<0.01), respectively. The CKD and CKD-DAPA rabbits showed a significantly reduced left ventricular ejection fraction when compared to the sham group (47.4±0.81 vs. 53.3±1.47 %; 48.41±1.50, both p<0.01), respectively. Baseline rhythm showed sinus rhythm in all rabbits and no spontaneous arrhythmias were found. The RR interval in the CKD group was significantly longer than those in the sham and CKD-DAPA groups (Figure A). The effective refractory period (ERP) of all cardiac chambers revealed no difference among those in the 3 groups, respectively (Figure B). In the atrial inducibility test, 2 rabbits in the CKD-DAPA group revealed inducible atrial arrhythmia. In the ventricular inducibility test, all rabbits revealed inducible ventricular arrhythmia (VA). The CKD group had a significantly higher VA inducibility than the sham (32.00±10.95 vs. 0.00±0.00 %, p<0.001) and CKD-DAPA (32.00±10.95 vs. 0.00±0.00 %, p<0.001) groups, respectively. The CKD group had a significantly larger area of fibrotic tissue than the sham and CKD-DAPA group (Figure C). The CKD-DAPA group had a significantly larger area of fibrotic tissue than the sham group (Figure C). Figure D demonstrated the collagen deposition (blue) in the myocardium in the 3 groups. Dapagliflozin led to decreased VA inducibility and reversed cardiac structural remodeling in CKD rabbits. Dapagliflozin potentially reduced the risk of arrhythmogenicity in cardiorenal syndrome.